Role of the Subunits Interactions in the Conformational Transitions in Adult Human Hemoglobin: an Explicit Solvent Molecular Dynamics Study

TL;DR

This study uses explicit solvent molecular dynamics to analyze the conformational transitions and subunit interactions in adult human hemoglobin, revealing stability differences and the T to R transition dynamics.

Contribution

It provides detailed insights into the molecular dynamics and structural stability of hemoglobin's different states, highlighting the role of subunit interactions in conformational changes.

Findings

R and R2 structures are stable with no quaternary changes within simulation time.

T structure exhibits flexibility and undergoes T to R transition.

Quaternary transition involves rotation at α1β2 and α2β1 interfaces.

Abstract

Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures, and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the sub-microsecond time scale, there is no marked difference in the global dynamics of the amino acids residues in both the oxy- and the deoxy- forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations while the T structure is dynamically more flexible and exhibited the T\rightarrow R quaternary conformational transition, which is propagated by the relative rotation of the residues at the {\alpha}1{\beta}2 and {\alpha}2{\beta}1 interface.